Proliferating cell nuclear antigen clamp associated factor, a potential proto-oncogene with increased expression in malignant gastrointestinal tumors

Gastrointestinal (GI) cancers, including malignancies in the gastrointestinal tract and accessory organs of digestion, represent the leading cause of death worldwide due to the poor prognosis of most GI cancers. An investigation into the potential molecular targets of prediction, diagnosis, prognosis, and therapy in GI cancers is urgently required. Proliferating cell nuclear antigen (PCNA) clamp associated factor (PCLAF), which plays an essential role in cell proliferation, apoptosis, and cell cycle regulation by binding to PCNA, is a potential molecular target of GI cancers as it contributes to a series of malignant properties, including tumorigenesis, epithelial-mesenchymal transition, migration, and invasion. Furthermore, PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer. In addition to GI cancers, PCLAF is also involved in other types of cancers and autoimmune diseases. Several pivotal pathways, including the Rb/E2F pathway, NF-κB pathway, and p53-p21 cascade, are implicated in PCLAF-mediated diseases. PCLAF also contributes to some diseases through dysregulation of the p53 pathway, WNT signal pathway, MEK/ERK pathway, and PI3K/AKT/mTOR signal cascade. This review mainly describes in detail the role of PCLAF in physiological status and GI cancers. The signaling pathways involved in PCLAF are also summarized. Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.